Supplemental support is requested for a hypertension research program (SCOR) that is based on identification of heterogeneity among hypertensive patients using hormonal measurements profiled in relation to electrolyte metabolism. These renin and aldosterone profiles are then related to clinical and physiological characteristics to identify causal mechanisms and to develop more specific and predictable treatments. Renin profiling of essential hypertension has also suggested differences in clinical course and prognosis. Our clinical and laboratory research has led us to develop the vasoconstriction-volume hypothesis for analysis and treatment of all hypertension. The hypothesis is strengthened by our recent studies using several angiotensin blockers which expose a broad role for renin in common hypertension and establish that renin measurements do reflect its involvement in blood pressure control. Thus, we can now quantify vasoconstriction and volume elements in each patient. In this supplement we propose to extend our biochemical and physiologic studies of "prorenin", a recently discovered inactive form of plasma renin. In other proposals the vasoconstriction volume hypothesis is used as a framework to examine further various facets of the hypertension problem in laboratory, clinical and general population research. In a dog model we propose to define the pressor interactions of angiotensin, aldosterone and sodium balance. In rabbits with two forms of renal hypertension we will examine the dynamic involvement of vasoconstriction and volume factors in sustaining hypertension and inducing vasculopathy and study the effects of specific blockade of the renin axis using our purified F'ab fragments to converting enzyme. We also propose to determine the incidence and features of our newly-discovered form of steroid hypertension in man. In addition we will relate the endocrine profiles of hypertensive patients to their baseline hemodynamic, catecholamine, and rheologic patterns, study the effects of angiotensin and beta blockade, and characterize variations in their blood pressure patterns as continuously recorded for days. We will also characterize the endocrine-sodium profiles of normal and toxemic pregnancy. Finally, our research-based treatment system will be critically tested in a general population.